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. 2006 Jun 12;203(6):1543-50.
doi: 10.1084/jem.20051711. Epub 2006 Jun 5.

The E delta enhancer controls the generation of CD4- CD8- alphabetaTCR-expressing T cells that can give rise to different lineages of alphabeta T cells

Iannis Aifantis  1 , Craig H Bassing, Annette I Garbe, Katie Sawai, Frederick W Alt, Harald von Boehmer
Affiliations

The E delta enhancer controls the generation of CD4- CD8- alphabetaTCR-expressing T cells that can give rise to different lineages of alphabeta T cells

Iannis Aifantis et al. J Exp Med. .

Erratum in

  • J Exp Med. 2006 Jul 10;203(7):1831

Abstract

It is well established that the pre-T cell receptor for antigen (TCR) is responsible for efficient expansion and differentiation of thymocytes with productive TCRbeta rearrangements. However, Ptcra- as well as Tcra-targeting experiments have suggested that the early expression of Tcra in CD4- CD8- cells can partially rescue the development of alphabeta CD4+ CD8+ cells in Ptcra-deficient mice. In this study, we show that the TCR E delta but not E alpha enhancer function is required for the cell surface expression of alphabetaTCR on immature CD4- CD8- T cell precursors, which play a crucial role in promoting alphabeta T cell development in the absence of pre-TCR. Thus, alphabetaTCR expression by CD4- CD8- thymocytes not only represents a transgenic artifact but occurs under physiological conditions.

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Figures

Figure 1.
Figure 1.
Vα2-enriched early αβ T cells in wt and Ptcra−/− mice. (A) TCRβ versus Vα2 FACS profile in thymi of wt and Ptcra −/− thymocytes. DN (CD4−CD8−) cells were electronically gated after the exclusion of CD4+, CD8+, and NK1.1 cells. (B) A CD4 versus CD8 profile of Ptcra −/− thymi. (C and D) Staining of Ptcra −/− thymocytes (total or CD4−CD8−) with TCRβ and Vα2 antibodies. Numbers in quadrants indicate the percentages of cells in that quadrant.
Figure 2.
Figure 2.
CD4−CD8− αβ T cells in the thymus and lymphoid periphery. (A) CD4,CD8 versus NK1.1 staining in the thymus of wt and CD1−/− mice (top). TCRβ versus Vα2 analysis of NK1.1− CD4−CD8− thymocytes (bottom). (B and C) Identification of peripheral CD4−CD8− TCRβ+ cells in the spleen and lymph nodes using TCRβ, Vα2, CD4, and CD8 antibody labeling. Numbers in quadrants indicate the percentages of cells in that quadrant.
Figure 3.
Figure 3.
Phenotype and developmental potential of early αβ T cells. (A) Vα2 versus TCRβ staining of Ptcra −/− ,Tcrd −/− thymocytes. (B) Phenotypic analysis of CD4−CD8− and CD4−CD8− TCRβ+ cells using CD44 and CD25 antibodies. (C) Embryonic day 14.5 fetal (Rag-1−/−) thymic organ culture of CD4−CD8− TCRβ+ NK1.1− Ptcra −/− cells. Cells were cultured for 7 d and were stained with Vα2, TCRβ, CD4, and CD8 antibodies. A CD4 versus CD8 staining of Vα2+ donor cells is also shown (bottom). Numbers in quadrants indicate the percentages of cells in that quadrant.
Figure 4.
Figure 4.
Eα controls late but not early development of αβ T cells. (A) Absolute cell numbers of Ptcra −/− and Ptcra −/− ,Eα−/− littermates. Error bars represent SD. (B) CD4 versus CD8 profiles of littermates belonging to all indicated genotypes. (C and D) Vα2 versus TCRβ antibody labeling in total DN thymocytes (C) and spleen cells (D). Numbers in quadrants indicate the percentages of cells in that quadrant.
Figure 5.
Figure 5.
Immature but not mature T cells from Eα−/− mice express diverse TCRα chains. (A) Staining of thymocytes from Ptcra −/− ,Eα+/+ and Ptcra −/− ,Eα−/− mice with CD4 and CD8 (top), and staining of CD4+CD8+ TCRβ+ cells with Vα3 + Vα8 + Vα11 antibodies versus Vα2 antibodies (middle). Bottom panel shows isotype controls for the staining in the middle panel. (B) Staining of NK1.1− CD4−CD8− TCRβ thymocytes from Ptcra −/− ,Eα+/+ and Ptcra −/− ,Eα−/− mice with Vα3 + Vα8 + Vα11 antibodies versus Vα2 antibodies (top) and with isotype controls (bottom). Numbers in quadrants indicate the percentages of cells in that quadrant.
Figure 6.
Figure 6.
Eγ is essential for pre-TCR–independent T cell development. (A) Absolute cell numbers of Ptcra −/− and Ptcra −/− ,Eδ−/− littermates. 4–8-wk-old mice were analyzed. Error bars represent SD. (B and C) CD4 versus CD8 (B) and TCRβ versus TCRγδ (C) profiles of littermate thymi. (D) Analysis of the DN compartment using CD25 and CD44 antibodies. Numbers in quadrants indicate the percentages of cells in that quadrant.
Figure 7.
Figure 7.
Absence of Vα2-expressing cells in the thymi of Ptcra−/−,Eγ−/− mice. TCRβ versus Vα2 staining of either total thymocytes (A) or CD4−CD8− cells (B) of littermate mice analyzed at 4 wk of age. Numbers in quadrants indicate the percentages of cells in that quadrant.
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